Structural prerequisites for the hypotensive action of parathyroid hormone

D. H. Ellison, D. A. McCarron

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22 Scopus citations

Abstract

We assessed the vascular, phosphaturic, and calcemic responses to several synthetic parathyroid hormone (PTH) analogues. Bovine (b) PTH (1-34), human (h) PTH (1-34), hPTH (53-84), [Nle8,Nle18,Tyr34]bPTH (1-34), and [Nle8,Nle18,Tyr34]bPTH (3-34) were administered in doses between 1 and 500 μg/kg as bolus intravenous injections to male Wistar-Kyoto rats aged 18-26 wk. Antagonism of the action of PTH was assessed in rats pretreated with 10 or 100 μg/kg [Nle8,Nle18,Tyr34]bPTH (3-34) followed by 10 μg/kg of bPTH (1-34), or with 10 μg/kg hPTH (53-84) followed by 10 μg/kg hPTH (1-34). Bovine PTH (1-34), hPTH (1-34), and [Nle8,Nle18,Tyr34]bPTH (1-34) produced virtually identical log dose-dependent hypotension, with 100 μg/kg of each analogue producing a 56% reduction in mean arterial pressure. Neither hPTH (53-84) nor [Nle8,Nle18,Tyr34]bPTH (3-34) demonstrated any effect on mean arterial pressure at doses up to 500 μg/kg. Pretreatment with the inactive analogues failed to antagonize the vasodilating response to either bPTH (1-34) or hPTH (1-34). The vasoactive analogues significantly increased urinary phosphorus excretion while the inactive analogues did not modify it. hPTH (1-34) produced a modest decrease in serum Ca2+ at 1 min after injection. The results document that the vasodilating effect of PTH is a specific action of the peptide. Deletion of the first two amino acid residues abolishes both the phosphaturic and hypotensive effects of the peptide. Acute changes in serum Ca2+ do not appear to be a prerequisite for the vasodilatory response. Inactive analogues of PTH do not antagonize the vascular actions of the peptide.

Original languageEnglish (US)
Pages (from-to)F551-F556
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume15
Issue number5
StatePublished - Jan 1 1984

ASJC Scopus subject areas

  • Physiology

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